Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15gene.[5]
Function
The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembraneglycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.[6]
Clinical significance
Arthritis
ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress.[7] ADAM15 also has an antiapoptotic effect in osteoarthriticchondrocytes.[8]
Cancer
The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues[9] Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels.[10] ADAM15 has also been shown to have a role in prostate cancer again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues[9] and also through its modulation of epithelial cell- tumour cell interactions.[11]
^Böhm B, Hess S, Krause K, Schirner A, Ewald W, Aigner T, Burkhardt H (May 2010). "ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis". Arthritis Rheum. 62 (5): 1372–82. doi:10.1002/art.27387. PMID20213810.
^Kleino I, Ortiz RM, Yritys M, Huovila AP, Saksela K (November 2009). "Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins". J. Cell. Biochem. 108 (4): 877–85. doi:10.1002/jcb.22317. PMID19718658. S2CID25997734.
Further reading
Primakoff P, Myles DG (2000). "The ADAM gene family: surface proteins with adhesion and protease activity". Trends Genet. 16 (2): 83–7. doi:10.1016/S0168-9525(99)01926-5. PMID10652535.
McKie N, Edwards T, Dallas DJ, et al. (1997). "Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes". Biochem. Biophys. Res. Commun. 230 (2): 335–9. doi:10.1006/bbrc.1996.5957. PMID9016778.
Nath D, Slocombe PM, Stephens PE, et al. (1999). "Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells". J. Cell Sci. 112 (4): 579–87. doi:10.1242/jcs.112.4.579. PMID9914169.
Kärkkäinen I, Karhu R, Huovila AP (2000). "Assignment of the ADAM15 gene to human chromosome band 1q21.3 by in situ hybridization". Cytogenet. Cell Genet. 88 (3–4): 206–7. doi:10.1159/000015549. PMID10828588. S2CID42541340.
Ham C, Levkau B, Raines EW, Herren B (2002). "ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin". Exp. Cell Res. 279 (2): 239–47. doi:10.1006/excr.2002.5606. PMID12243749.
